A Phase I Study of the CXCR-4 Inhibitor AMD3100 for the Treatment of Neutropenia Due to Mutations of CXCR-4, the Myelokathexis Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Blood Neutrophil Counts.
研究概览
简要总结
This is an initial study to determine if CXCR4 inhibitor AMD 3100 or plerixafor may be a potential treatment for neutropenia due to CXCR4 mutations, the myelokathexis or WHIM (warts, hypogammaglobulinemia, immunodeficiency and myelokathexis) syndrome. This is the initial study of this concept and will involve up to 6 patients to receive increasing doses of plerixafor administered subcutaneously or on an alternate day basis. It is unknown if these patients will be highly sensitive to a blockade of CXCR4 activity and release more white blood cells than normal volunteers or cancer patients given the same dose of this drug. Therefore doses will begin at a level 12 fold less than currently used to mobilize stem cells and will be increased stepwise to achieve an acceptable circulating level of neutrophils.
详细描述
This is an open label, single Center, phase I study to examine the hematological effects, pharmacokinetics and safety of plerixafor in patients with myelokathexis attributable to mutations of CXCR4, utilizing serial, escalating doses of plerixafor administered on days 1, 3, 5, 8, and 10. Five intrapatient escalating dose levels, 20 micrograms per kilogram (mcg/kg), 40 micrograms/kilogram(mcg/kg), 80 micrograms/kilogram(mcg/kg), and 240 micrograms/kilogram (mcg/kg)will be examined. The subjects will be patients at the University of Washington General Clinical Research Center for up to 10 days; the study requires subject be available for up to 14 days. Patients will be monitored for hematological effects of plerixafor and observed for adverse effects. If a normal blood neutrophil count is achieved and maintained for at least 24 hours prior to the highest dose, we will stop at that level.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age over 18 years, WBC (white blood count) less than 3.0 x 10^9 per Liter,
- •Absolute neutrophil count less than 2.0 x 10^9 per Liter,
- •platelets greater than 100 x 10^6 per Liter, creatinine less than 2.0/milligrams per/deciliter,
- •Creatinine clearance > 60 ml/min calculated,
- •Aspartate Aminotransferase-GOT (SGOT), Alanin Aminotransferase-GPT (SGPT), bilirubin < 2.5 upper limit of normal,
- •Eastern Cooperative Oncology Group (ECOG) status 0 or 1,
- •mutation identified and confirmed in CXCR4,
- •on no granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF) within 3 weeks of the study drug
- •patient signs consent, accepts contraception
排除标准
- •greater than 18 years of age,
- •sensitivity to plerixafor,
- •pregnant,
- •prisoner,
- •decisionally impaired,
- •judged unlikely to comply,
- •illness that may interfere with interpretation of results,
- •leukemia,
- •malignancy,
- •active infection requiring antibiotics within one week of study drug administration,
- •history of cardiac conduction or electrocardiogram (EKG) abnormality,
- •previous experimental therapy within one week.
研究组 & 干预措施
AMD3100 or plerixafor
SINGLE arm study with increasing doses of Plerixafor
干预措施: AMD3100 or plerixafor (Drug)
结局指标
主要结局
Blood Neutrophil Counts.
时间窗: up to 14 days, depending on when subject reached peak response, i.e., the highest count after the stimulus (plerixafor)
Effectiveness of drug based on increases of blood neutrophil counts to greater than 2.0 x 10\^9 per liter
次要结局
未报告次要终点
研究者
David Dale
Professor
University of Washington